Multiscale approach to investigate self-assembly of telodendrimer based nanocarriers for anticancer drug delivery.
Multiscale approach to investigate self-assembly of telodendrimer based nanocarriers for anticancer drug delivery.
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DOI：
10.1021/la503949b
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发表时间：
2015-04-14
期刊：
影响因子：
--
通讯作者：
Nangia S
中科院分区：
文献类型：
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作者：
Jiang W;Luo J;Nangia S
难溶抗癌药物的传递可以通过使用聚合物药物传递系统来实现，能够形成稳定的自组装纳米载体，药物被包裹在其疏水核心中。计算研究可以帮助设计高效的药物输送平台；然而，纳米载体自组装过程的模拟是具有挑战性的，因为与大系统规模(数百万个原子)和长时间尺度的平衡所需的高计算成本相关。在这项工作中，我们通过使用多尺度计算方法并结合实验来分析单个构建块在高度可调的线性聚乙二醇-b-树枝状低聚(胆酸)嵌段共聚物端胶树枝状分子自组装中的作用，从而克服了这一挑战。多尺度方法包括开发端树突体的粗粒度描述，在几微秒内进行模拟以捕获自组装过程，然后将粗粒度系统反向映射到原子表示以进行结构分析。克服了计算瓶颈，我们可以运行多个自组装模拟，并确定平均尺寸、药物-端粒胶束化学计量比、最佳载药量以及纳米载体的氢键和溶剂可及区域等原子细节。计算结果与实验数据吻合较好，说明了多尺度方法的成功。
Delivery of poorly soluble anticancer drugs can be achieved by employing polymeric drug delivery systems, capable of forming stable self-assembled nanocarriers with drug encapsulated within their hydrophobic cores. Computational investigations can aid the design of efficient drug-delivery platforms; however, simulations of nanocarrier self-assembly process are challenging due to high computational cost associated with the large system sizes (millions of atoms) and long time scales required for equilibration. In this work, we overcome this challenge by employing a multiscale computational approach in conjunction with experiments to analyze the role of the individual building blocks in the self-assembly of a highly tunable linear poly(ethylene glycol)-b-dendritic oligo(cholic acid) block copolymer called telodendrimer. The multiscale approach involved developing a coarse grained description of the telodendrimer, performing simulations over several microseconds to capture the self-assembly process, followed by reverse mapping of the coarse grained system to atomistic representation for structural analysis. Overcoming the computational bottleneck allowed us to run multiple self-assembly simulations and determine average size, drug-telodendrimer micellar stoichiometry, optimal drug loading capacity, and atomistic details such hydrogen-bonding and solvent accessible area of the nanocarrier. Computed results are in agreement with the experimental data, highlighting the success of the multiscale approach applied here.